The proposal is a competitive continuation of an original grant that has led to the clinical application of inhaled nitric oxide (NO) for the treatment of pulmonary hypertension. Inhaled NO will produce selective pulmonary vasodilation IN VENTILATED alveoli in some 60% of individuals without causing a fall in arterial oxygen saturation. However, 40% of patients do noT responD to NO. The investigators will study the roles of oxygen radicals and eicosanoids in hyporesponsiveness to NO. They will determine the relationship of loss of responsiveness to NO and the loss of hypoxic pulmonary vasoconstriction (HPV) in sepsis, especially as it may relate to inducible No synthase. Lastly, they will study inhalation therapy with agents that do not affect HPV and see if they are effective in enhancing gas exchange in ovine and murine lung injury models.